• Sleep Disorders Project

Sleep Disorders Project

Research on sleep disorders; understand the etiology and pathophysiology

Project Leader Makoto Honda

Project Leader
Makoto Honda

Research Summary

Our goal is to find the causes and develop better treatments for Narcolepsy and Hypersomnia.

Narcolepsy is a sleep disorder of abnormal intrinsic sleep-wake regulation, resulting in unique symptoms including frequent lapses into sleep, nocturnal sleep instability, and REM sleep related manifestations such as cataplexy (abrupt loss of muscle tone triggered by emotion), sleep paralysis, and hypnagogic hallucination.

Narcolepsy is associated with a deficiency of wake-promoting orexin/hypocretin producing neurons localized in the hypothalamus, and virtually all the patients carry human leukocyte antigen (HLA)-DQB1*06:02.

We are trying to solve the mystery of narcolepsy

Narcolepsy is associated with a variety of physical and psychiatric comorbid conditions. Since appropriate wakefulness is essential for higher brain functions, abnormal sleep-wake regulation can lead to various associated features. Despite the progress in sleep research fields, we currently have inadequate symptom-based treatments for sleep disorders, including narcolepsy. We are trying to elucidate the pathophysiology of narcolepsy with multifaceted problems to improve the QOL of hypersomnia patients.

Selected Publications

  • Natsubori A et al. (2022) Serotonergic neurons control cortical neuronal intracellular energy dynamics by modulating astrocyte-neuron lactate shuttle iScience 26, 105830, 2023 doi: 10.1016/j.isci.2022.105830.
  • Miyagawa T, et al (2022) A rare genetic variant in the cleavage site of prepro-orexin gene is associated with idiopathic hypersomnia. npj Genomic Medicine 7:29 [2022/4/12]
  • Honda M, et al (2022) Low carnitine palmitoyltransferase 1 activity is a risk factor for narcolepsy type 1 and other hypersomnia. Sleep 45:zsac160
  • Miyagawa T, et al (2022) A variant in orexin receptor-2 is associated with self-reported daytime sleepiness in the Japanese population. J Hum Genetics 67:377-380
  • Honda M, et al (2021) Evaluation of pathological sleepiness by Multiple Sleep Latency Test and 24-hour polysomnography in patients suspected of idiopathic hypersomnia Psychiatry Clin Neurosci 75:149-151
  • Natsubori A,et al (2020) “In vivo state-dependent dynamics of cellular energy status in cortical neurons”. Communications Biol 3 491
  • Shimada M et al. (2020) “Epigenome-wide association study of narcolepsy-affected lateral hypothalamic brain and overlapping DNA methylation profiles between narcolepsy and multiple sclerosis”. Sleep 43(1):zsz198
  • Shimada M, et al (2020) Metabolome analysis using cerebrospinal fluid from narcolepsy type 1 patients. Sleep. 43:zsaa095.